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Federal Court Determines the Inventive Concept of an Improved Drug Formulation

In this Federal Court decision (per Pentney J.), the plaintiffs Allergan and AbbVie (“Allergan”) were successful in upholding the validity of their 691 Patent. The defendant (“Juno”) conceded that its proposed generic drug product would infringe the 691 Patent. The main issues before the Court were obviousness and sufficiency.

Allergan v Juno, 2023 FC 1686

The 691 Patent claims a pharmaceutical composition that covers Allergan’s drug product, LUMIGAN RC, which is used to treat glaucoma and intra-ocular hypertension (“IOH”) through lowering intraocular pressure (“IOP”). LUMIGAN RC is an improvement over a previous formulation (“Old LUMIGAN”).

LUMIGAN RC has two key features compared to Old LUMIGAN: a significant reduction of the active ingredient bimatoprost; and a significant increase in the preservative benzalkonium chloride (“BAK”).

At trial, Allergan asserted two claims of the 691 Patent (with most of the focus on Claim 16):

Claim 16: A composition comprising by weight 0.01% bimatoprost, 0.02% benzalkonium chloride, 0.268% sodium phosphate dibasic heptahydrate, 0.014% citric acid monohydrate, 0.81% sodium chloride, water, and wherein said composition is an aqueous liquid with a pH adjusted to 7.3.

Claim 19: Use of a composition according to any one of claims 1 to 16 for treating glaucoma or intraocular hypertension in a mammal.

Pentney J. applied the four-step obviousness test from Sanofi SCC. At the first step of the test, Pentney J. identified the skilled person as a team comprised of an ophthalmologist and a formulator, and discussed the common general knowledge of the skilled person.

At the second step of the Sanofi test, Pentney J. identified the inventive concept – which was a key point of contention between the parties. Juno argued that the inventive concept was clear from the wording of the claims alone, and that it was simply the new formulation itself. Allergan disagreed and argued that it was necessary to look to the description to understand the inventive concept because the inventive concept was not readily apparent from the text of the claims (which were merely directed to a formulation per se), relying on the Federal Court of Appeal’s decision in Shire (2021 FCA 52). Pentney J. agreed with Allergan and, based on the description of the invention, including the examples in the patent, construed the inventive concept of Claim 16 as consisting of three elements: 1) a decreased bimatoprost concentration; 2) an increased BAK concentration; and 3) achieving equal or greater IOP reduction with the new formulation as was achieved by the old formulation.

At the third step of the Sanofi test, Pentney J. determined that there was a significant gap between the state of the art and the inventive concept, and that it would not have been obvious to the skilled person to bridge the gap. This analysis was broken down to the individual elements of the inventive concept:

1. Decreased bimatoprost
Pentney J. found that the prior art taught away from decreasing the concentration of bimatoprost because the prior art taught that doing so was correlated with decreased IOP reduction, which was contrary to the most important goal in treating glaucoma and IOH.

Juno argued that, despite these teachings, the prior art showed that the bimatoprost concentration can be reduced while maintaining a clinically effective reduction of IOP in patients. Pentney J. rejected this argument, finding that the skilled person would look for medication that could provide the same level of IOP reduction as the “first-line treatment” available in the relevant period.

2. Increased BAK
Pentney J. found that the prior art taught away from increasing BAK. BAK was known to be cytotoxic and there was a trend (at least in Canada and the US) toward moving away from using BAK, even though it was commonly used as a preservative in eye drop medications. The prior art taught that it was desirable to reduce BAK to decrease harmful effects (some of which are irreversible), especially when those effects could accumulate through chronic treatments.

3. Achieving equal or greater IOP reduction
Pentney J. considered whether the prior art taught that increasing BAK would offset the expected reduction in efficacy from reducing bimatoprost. Juno argued that this was the case because BAK was known to increase ophthalmic drugs’ penetration through the cornea to increase efficacy. Despite the many pieces of prior art cited by Juno, Pentney J. agreed with Allergan’s more nuanced view that although BAK was known to increase corneal permeability for some types of drug molecules, it was not known to increase permeability for lipophilic molecules like bimatoprost. Therefore, the state of the art would not have taught the skilled formulator that IOP reduction could be maintained or enhanced by increasing BAK concentrations.

At the fourth step of the Sanofi test, Pentney J. found that Allergan’s invention was not obvious to try. Juno argued that the skilled person would have been motivated to refine the existing formulation of Old LUMIGAN to reduce side effects while maintaining clinical efficacy because the prior art taught that the bimatoprost concentration could be reduced while maintaining a clinically effective level of IOP reduction. Juno also argued that BAK was known to be a corneal penetration enhancer, so it would have been a “natural step” to increase BAK concentrations to offset decreases in bimatoprost. Any uncertainties about clinical efficacy would have been resolved through routine testing. Pentney J. disagreed and held that the prior art taught away from the elements of the inventive concept. Also, Allergan’s “course of conduct” evidence showed that the development of LUMIGAN RC was not routine or straightforward.

Juno argued that the 691 Patent failed to provide sufficient disclosure, including with respect to the new formulation’s safety, efficacy, and scientific basis.  Pentney J. disagreed.

The components of the new formulation were commonly used and well-known at the relevant date, and there was no evidence suggesting that the skilled person would have had difficulty administering the patented formulation to glaucoma or IOH patients. There was also sufficient disclosure to enable the skilled person to make the new formulation.

The absence of safety information was irrelevant to the patent’s validity, as there was no evidence to suggest toxicity in humans and the standards of disclosure for obtaining a patent are not the same as the standards for obtaining regulatory approval.

Pentney J. reaffirmed that there is no requirement for patents to expressly state the problem to be solved or the scientific rationale for why the invention works. Although the underlying motivation of the new formulation was to reduce a side effect (hyperemia) of the old formulation, the 691 Patent did not make claims to that effect and therefore did not have to make a disclosure about it. In any event, the 691 Patent made sufficient disclosure with respect to the efficacy of BAK as a corneal penetration enhancer and the predicted effect of the new drug on humans (based on rabbit studies, which are regularly used as a basis for prediction).

In conclusion, the 691 Patent was not invalid for obviousness or insufficient disclosure.